Synthesis and Antiproliferative Screening Of Novel Analogs of Regioselectively Demethylated Colchicine and Thiocolchicine

Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry
Dominika CzerwonkaAdam Huczyński

Abstract

Colchicine, a pseudoalkaloid isolated from Colchicumautumnale, has been identified as a potent anticancer agent because of its strong antimitotic activity. It was shown that colchicine modifications by regioselective demethylation affected its biological properties. For demethylated colchicine analogs, 10-demethylcolchicine (colchiceine, 1) and 1-demethylthiocolchicine (3), a series of 12 colchicine derivatives including 5 novel esters (2b-c and 4b-d) and 4 carbonates (2e-f and 4e-f) were synthesized. The antiproliferative activity assay, together with insilico evaluation of physicochemical properties, confirmed attractive biological profiles for all obtained compounds. The substitutions of H-donor and H-acceptor sites at C1 in thiocolchicine position provide an efficient control of the hydration affinity and solubility, as demonstrated for anhydrate 3, hemihydrate 4e and monohydrate 4a.

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Citations

May 21, 2020·Journal of Medicinal Chemistry·Iuliia A GrachevaAlexey Yu Fedorov
Dec 23, 2020·The Journal of Organic Chemistry·Dominika CzerwonkaAdam Huczyński

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Methods Mentioned

BETA
X-ray
NMR
co-crystallization

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